PROJECT SUMMARY/ABSTRACT. Telomere diseases encompass a spectrum of rare and fatal syndromes caused by mutations in genes regulating telomere biology. These include the severe childhood blood disorder dyskeratosis congenita (DC) and later-onset lung diseases such as pulmonary fibrosis (PF). Despite progress in gene and pathway discovery in the past two decades, there has been no translation of this knowledge into therapies, and there are no curative treatments. Central to the pathogenesis of telomere diseases is disruption of telomerase, the ribonucleoprotein complex that replenishes telomeres in human cells. The long-term goal of this project is to therapeutically restore the long non-coding RNA component of telomerase, TERC, which is dysregulated in DC, PF and other telomere diseases. The